What do cancer-specific T cells 'see'?
| Autor: | Shah S; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Al-Omari A; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Cook KW; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Paston SJ; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Durrant LG; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK.; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Brentville VA; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Discovery immunology [Discov Immunol] 2022 Dec 06; Vol. 2 (1), pp. kyac011. Date of Electronic Publication: 2022 Dec 06 (Print Publication: 2023). |
| DOI: | 10.1093/discim/kyac011 |
| Abstrakt: | Complex cellular interactions between the immune system and cancer can impact tumour development, growth, and progression. T cells play a key role in these interactions; however, the challenge for T cells is to recognize tumour antigens whilst minimizing cross-reactivity with antigens associated with healthy tissue. Some tumour cells, including those associated with viral infections, have clear, tumour-specific antigens that can be targeted by T cells. A high mutational burden can lead to increased numbers of mutational neoantigens that allow very specific immune responses to be generated but also allow escape variants to develop. Other cancer indications and those with low mutational burden are less easily distinguished from normal tissue. Recent studies have suggested that cancer-associated alterations in tumour cell biology including changes in post-translational modification (PTM) patterns may also lead to novel antigens that can be directly recognized by T cells. The PTM-derived antigens provide tumour-specific T-cell responses that both escape central tolerance and avoid the necessity for individualized therapies. PTM-specific CD4 T-cell responses have shown tumour therapy in murine models and highlight the importance of CD4 T cells as well as CD8 T cells in reversing the immunosuppressive tumour microenvironment. Understanding which cancer-specific antigens can be recognized by T cells and the way that immune tolerance and the tumour microenvironment shape immune responses to cancer is vital for the future development of cancer therapies. Competing Interests: KWC, VAB, and LGD have ownership interest in a patent. LD is a director and shareholder in Scancell Ltd. All authors are employees of Scancell Ltd. (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.) |
| Databáze: | MEDLINE |
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